Sickle cell disease is a hereditary hemolytic anemia in which the disease process is well understood at the molecular level: it is known that the abnormality which lies in the beta-6-glutamyl is substituted by a hydrophobic residue, valyl; in Hb S, by an abnormal hemoglobin. Observations reported from many laboratories are consistent with an aggregation mechanism due to hydrophobic interactions by deoxy Hb S, as postulated by Murayama. Recently we have found that both aggregation and solubility of deoxy Hb S are inhibited by inorganic ions in the order of the classical Hofmeister series. We also suspected and then found that red cells increase in volume upon "sickling." This change is opposite in direction to published claims. This volume increase was observed by Murayama in his high hydrostatic pressure exppriment - cells became spherical under high hydrostatic pressure, reversibly. And this is also consistent with Murayama's thermodynamic prediction of the volume of activation for Hb S. Upon oxygenation Hb S polymers are depolymerized exposing electrically charged groups thus increasing the conductance - also the electrically charged groups give rise to electrostriction; this causes red cells to shrink on "desckling", and conversely.